Synthesis and biological activity of the metabolites of diethyl 4-[(4-bromo-2-cyanophenyl)carbamoyl]benzylphosphonate (NO-1886)

Chem Pharm Bull (Tokyo). 1996 Mar;44(3):547-51. doi: 10.1248/cpb.44.547.

Abstract

Five metabolites of diethyl 4-[(4-bromo-2-cyanophenyl)carbamoyl]benzylphosphonate (NO-1886) (1) were synthesized to confirm their proposed structures. The metabolites (2-6) were found to be identical with the synthesized compounds. These metabolites were orally administered to Triton WR-1339-induced hypertriglyceridemic rats, and the plasma levels of triglycerides were measured to estimate lipoprotein lipase activity. All the metabolites showed lower potency than NO-1886.

MeSH terms

  • Animals
  • Benzamides / chemistry
  • Benzamides / pharmacokinetics*
  • Benzamides / pharmacology*
  • Biotransformation
  • Chromatography, High Pressure Liquid
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacokinetics*
  • Enzyme Inhibitors / pharmacology*
  • Hyperlipidemias / blood
  • Hyperlipidemias / chemically induced
  • Hyperlipidemias / drug therapy
  • Lipoprotein Lipase / antagonists & inhibitors*
  • Magnetic Resonance Spectroscopy
  • Male
  • Organophosphorus Compounds / chemistry
  • Organophosphorus Compounds / pharmacokinetics*
  • Organophosphorus Compounds / pharmacology*
  • Polyethylene Glycols
  • Rats
  • Rats, Sprague-Dawley
  • Triglycerides / blood

Substances

  • Benzamides
  • Enzyme Inhibitors
  • Organophosphorus Compounds
  • Triglycerides
  • 4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide
  • Polyethylene Glycols
  • Lipoprotein Lipase
  • tyloxapol